Evolutionary pathways of N2 neuraminidases of swine and human influenza A viruses: origin of the neuraminidase genes of two reassortants (H1N2) isolated from pigs

Abstract

The complete nucleotide sequences of the neuraminidase (NA) genes of two reassortant (H1N2) and two H3N2 influenza A viruses isolated from pigs were determined and phylogenetic relationships between these and previously reported N2 NA genes were investigated. On the basis of pairwise nucleotide sequence identity, the NA genes of two reassortants, A/sw/Kanagawa/2/78 and A/sw/Ehime/1/80, were most closely related to those of human influenza A virus strains isolated in 1972 and the earliest available swine H3N2 influenza A viruses, respectively. Phylogenetic trees showed that the NA genes can be segregated into three groups, including lineages for (i) swine strains, (ii) the earliest human strain and (iii) recent human strains. The evolutionary tree for the 11 nucleotide and amino acid sequences suggested that the NAs of A/sw/HK/4/76 and A/sw/Kanagawa/2/78 belong to the lineage for recent human viruses. In contrast, the NA genes of the A/sw/HK/3/76 and H1N2 reassortant A/sw/Ehime/1/80 viruses were found to be of a swine lineage. The swine virus NA genes were further characterized by the cocirculation of two distinct lineages. Although the rates of synonymous (silent) substitutions for the swine and human viruses were nearly identical (0.00946 to 0.00884 per site per year), the rate of non-synonymous (amino acid changing) substitutions for swine virus NA genes was about 60% of that for the human virus.